American Association for Cancer Research
mcr-23-0810_supplementary_table_s5_suppst5.xlsx (359.81 kB)

Supplementary Table S5 from PIGA Mutations and Glycosylphosphatidylinositol Anchor Dysregulation in Polyposis-Associated Duodenal Tumorigenesis

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posted on 2024-06-04, 07:41 authored by Elena Meuser, Kyle Chang, Angharad Walters, Joanna J. Hurley, Hannah D. West, Iain Perry, Matthew Mort, Laura Reyes-Uribe, Rebekah Truscott, Nicholas Jones, Rachel Lawrence, Gareth Jenkins, Peter Giles, Sunil Dolwani, Bilal Al-Sarireh, Neil Hawkes, Emma Short, Geraint T. Williams, Melissa W. Taggart, Kim Luetchford, Patrick M. Lynch, Diantha Terlouw, Maartje Nielsen, Sarah-Jane Walton, Andrew Latchford, Susan K. Clark, Julian R. Sampson, Eduardo Vilar, Laura E. Thomas

A VCF file containing putatively pathogenic variants found in 1142 intestinal cancer associated genes in 21 of the duodenal adenomas studied here (see supplementary table 1 for sample details). Full genomic datasets for these samples are available through EGA under accession: EGAD00001009332.


Health and Care Research Wales (HCRW)

National Institutes of Health (NIH)



The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA. PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.

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